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Combination Therapy for Migraines
Posted: February 2004  
Neurology Reviews / January 2004

A retrospective analysis of unpublished antimigraine drug trials found the combination of sumatriptan and a nonsteroidal anti-inflammatory drug (NSAID) produced the fastest and greatest relief of both migraine pain and the associated symptoms at four hours posttreatmet. A second trial found the combination of acetaminophen (500 mg), aspirin (500 mg), and caffeine (130 mg) was superior to sumatriptan (50 mg) alone for the early treatment of migraine. The results of both trials were reported at the 11th Congress of the International Headache Society.

In his presentation on sumatriptan combined with an NSAID, Ninan T. Mathew, MD, Director of the Houston Headache Clinic, said results were based on a meta-analysis of data from double-blind, randomized, placebo-controlled clinical trials in migraine patients treated with the oral NSAID naproxen, sumatriptan, combination NSAID and sumatriptan, combination NSAID and antiemetic, or subcutaneous dihydroergotamine. Patients were given a single dose of medication.

There were about 300 patients in each of three studies reviewed in the meta-analysis, Dr. Mathew said. The report compared the various therapies on both the pain of migraine and associated symptoms of nausea, photophobia, and phonophobia.

The investigators found that a combination of naproxen and sumatriptan was significantly better than other active treatments and placebo in terms of pain response at 1.5 hours after dosing. The other treatments resulted in a pain response for about 37% of patients, compared with nearly 50% of patients taking the combination therapy.

For nausea, only the naproxen/sumatriptan combination was significantly more effective than placebo at 2.5 hours after dosing, the investigators noted, while for both photophobia and phonophobia, only the combination therapy was significantly more effective than placebo at 1.5 hours. The percentage of patients with photophobia at 1.5 hours with the combination was about 55% compared to about 62% or more with the other treatments. The percentage of patients with phonophobia at 1.5 hours was about 48% with the combination therapy compared with 58% or more for the other treatments.

The researchers concluded that pain responded faster than any other symptom to any of the treatments, and nausea was slower to subside than pain with active treatment, suggesting there may be differing mechanisms for migraine pain and associated nausea. Dr. Mathew said the results indicate that "targeting more than one mechanism of pain is crucial in treating moderate to severe migraine."

In a trial combining acetaminophen, aspirin, and caffeine, Stephen D. Silberstein, MD, Director of the Jefferson Headache Center in Philadelphia, and colleagues at eight US centers compared single doses of acetaminophen, aspirin, and caffeine with sumatriptan. The trial was a randomized, double-blind, placebo-controlled study. The acetaminophen, aspirin, and caffeine group had 69 patients, the sumatriptan group had 67, and 35 patients received placebo. The study medication was to be taken at the first sign of a migraine episode.

The investigators reported that acetaminophen, aspirin, and caffeine was superior to 50 mg. of sumatriptan for pain intensity difference at four hours after dosing. More participants receiving acetaminophen, aspirin, and caffeine responded at two hours than did participants receiving sumatriptan (87% vs. 75%); 24-hour sustained response was also better among those receiving acetaminophen, aspirin, and caffeine than those receiving sumatriptan (66% vs. 49%). Participants reported no serious adverse events.

In this less-disabled migraine population, acetaminophen, aspirin, and caffeine taken at the first sign of migraine provided significantly earlier, superior, sustained pain relief, with rescue medication required less often compared with sumatriptan, the researches concluded. "If corroborated by additional data, these findings could help assure both physicians and patients that acetaminophen, aspirin, and caffeine provides benefits comparable to those of the leading prescription migraine product in the treated population", Dr. Silberstein reported.